| Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease. | |
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MedLine Citation:
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PMID: 20144646 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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LRRK2 mutations are recognized as the most frequent genetic cause of both familial and sporadic parkinsonism identified to date. A remarkable feature of this form of parkinsonism is the variable penetrance of symptom manifestation resulting in a wide range of age-at-onset in patients. Herein we use a functional approach to identify the Lrrk1 protein as a potential disease modifier demonstrating an interaction and heterodimer formation with Lrrk2. In addition, evaluation of LRRK1 variants in our large Lrrk2 p.G2019S-parkinsonism series from a Tunisian (n=145) identified a missense mutation (p.L416M) resulting in an average 6.2 years younger age at disease onset. In conclusion we show that the interaction of Lrrk1-Lrrk2 can form protein dimers and this interaction may influence the age of symptomatic manifestation in Lrrk2-parkinsonism patients. |
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Authors:
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Justus C Dachsel; Kenya Nishioka; Carles Vilariño-Güell; Sarah J Lincoln; Alexandra I Soto-Ortolaza; Jennifer Kachergus; Kelly M Hinkle; Michael G Heckman; Barbara Jasinska-Myga; Julie P Taylor; Dennis W Dickson; Rachel A Gibson; Faycal Hentati; Owen A Ross; Matthew J Farrer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-06 |
Journal Detail:
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Title: Mechanisms of ageing and development Volume: 131 ISSN: 1872-6216 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-29 Completed Date: 2010-06-29 Revised Date: 2013-05-30 |
Medline Journal Info:
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Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
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Languages: eng Pagination: 210-4 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. daechsel.justus@mayo.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Age of Onset Humans Mutation Parkinson Disease / genetics* Parkinsonian Disorders / genetics* Penetrance Protein Multimerization / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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P50 NS040256/NS/NINDS NIH HHS; P50 NS040256-109002/NS/NINDS NIH HHS; P50 NS40256/NS/NINDS NIH HHS; R21 NS064885-01/NS/NINDS NIH HHS; R21 NS64885/NS/NINDS NIH HHS |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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